Lisa E. Hines

Potentially Harmful Drug–Drug Interactions in the Elderly: A Review

BACKGROUND Elderly patients are vulnerable to drug interactions because of age-related physiologic changes, an increased risk for disease associated with aging, and the consequent increase in medication use. OBJECTIVE The purpose of this narrative review was to describe findings from rigorously designed observational cohort and case-control studies that have assessed specific drug interactions in elderly patients. METHODS The PubMed and International Pharmaceutical Abstracts databases were searched for studies published in English over the past 10 years (December 2000-December 2010) using relevant Medical Subject Headings terms (aged; aged, 80 and over; and drug interactions) and search terms (drug interaction and elderly). Search strategies were saved and repeated through September 2011 to ensure that the most recent relevant published articles were identified. Additional articles were found using a search of review articles and reference lists of the identified studies. Studies were included if they were observational cohort or case-control studies that reported specific adverse drug interactions, included patients aged ≥65 years, and evaluated clinically meaningful end points. Studies were excluded if they used less rigorous observational designs, assessed pharmacokinetic/pharmacodynamic properties, evaluated drug-nutrient or drug-disease interactions or interactions of drug combinations used for therapeutic benefit (eg, dual antiplatelet therapy), or had inconclusive evidence. RESULTS Seventeen studies met the inclusion criteria. Sixteen studies reported an elevated risk for hospitalization in older adults associated with adverse drug interactions. The drug interactions included: angiotensin-converting enzyme (ACE) inhibitors and potassium-sparing diuretics, ACE inhibitors or angiotensin receptor blockers and sulfamethoxazole/trimethoprim, benzodiazepines or zolpidem and interacting medications, calcium channel blockers and macrolide antibiotics, digoxin and macrolide antibiotics, lithium and loop diuretics or ACE inhibitors, phenytoin and sulfamethoxazole/trimethoprim, sulfonylureas and antimicrobial agents, theophylline and ciprofloxacin, and warfarin and antimicrobial agents or nonsteroidal anti-inflammatory drugs. One study reported the risk for breast cancer-related death as a function of paroxetine exposure among women treated with tamoxifen. CONCLUSIONS Several population-based studies have reported significant harm associated drug interactions in elderly patients. Increased awareness and interventions aimed at reducing exposure and minimizing the risks associated with potentially harmful drug combinations are needed.

Recommendations to Improve the Usability of Drug-Drug Interaction Clinical Decision Support Alerts

OBJECTIVE To establish preferred strategies for presenting drug-drug interaction (DDI) clinical decision support alerts. MATERIALS AND METHODS A DDI Clinical Decision Support Conference Series included a workgroup consisting of 24 clinical, usability, and informatics experts representing academia, health information technology (IT) vendors, healthcare organizations, and the Office of the National Coordinator for Health IT. Workgroup members met via web-based meetings 12 times from January 2013 to February 2014, and two in-person meetings to reach consensus on recommendations to improve decision support for DDIs. We addressed three key questions: (1) what, how, where, and when do we display DDI decision support? (2) should presentation of DDI decision support vary by clinicians? and (3) how should effectiveness of DDI decision support be measured? RESULTS Our recommendations include the consistent use of terminology, visual cues, minimal text, formatting, content, and reporting standards to facilitate usability. All clinicians involved in the medication use process should be able to view DDI alerts and actions by other clinicians. Override rates are common but may not be a good measure of effectiveness. DISCUSSION Seven core elements should be included with DDI decision support. DDI information should be presented to all clinicians. Finally, in their current form, override rates have limited capability to evaluate alert effectiveness. CONCLUSION DDI clinical decision support alerts need major improvements. We provide recommendations for healthcare organizations and IT vendors to improve the clinician interface of DDI alerts, with the aim of reducing alert fatigue and improving patient safety.

Consensus recommendations for systematic evaluation of drug-drug interaction evidence for clinical decision support.

BackgroundHealthcare organizations, compendia, and drug knowledgebase vendors use varying methods to evaluate and synthesize evidence on drug–drug interactions (DDIs). This situation has a negative effect on electronic prescribing and medication information systems that warn clinicians of potentially harmful medication combinations.ObjectiveThe aim of this study was to provide recommendations for systematic evaluation of evidence for DDIs from the scientific literature, drug product labeling, and regulatory documents.MethodsA conference series was conducted to develop a structured process to improve the quality of DDI alerting systems. Three expert workgroups were assembled to address the goals of the conference. The Evidence Workgroup consisted of 18 individuals with expertise in pharmacology, drug information, biomedical informatics, and clinical decision support. Workgroup members met via webinar 12 times from January 2013 to February 2014. Two in-person meetings were conducted in May and September 2013 to reach consensus on recommendations.ResultsWe developed expert consensus answers to the following three key questions. (i) What is the best approach to evaluate DDI evidence? (ii) What evidence is required for a DDI to be applicable to an entire class of drugs? (iii) How should a structured evaluation process be vetted and validated?ConclusionEvidence-based decision support for DDIs requires consistent application of transparent and systematic methods to evaluate the evidence. Drug compendia and clinical decision support systems in which these recommendations are implemented should be able to provide higher-quality information about DDIs.

Warfarin Interactions With Substances Listed in Drug Information Compendia and in the FDA-Approved Label for Warfarin Sodium

Interactions of warfarin with other drugs or substances can pose a serious problem. We assessed three drug information compendia—Clinical Pharmacology, ePocrates, and Micromedex—and the warfarin sodium (Coumadin) product label (August 2007) approved by the US Food and Drug Administration for listings of interactions between warfarin and drugs, biologics, foods, and dietary supplements. The drug information compendia and warfarin label differed greatly as to the total number of substances that interact with warfarin. Of a total of 648 entries from the four sources, only 50 were common to all the sources. The types of substances listed as interacting with warfarin were entire classes of drugs, individual drugs, and combinations; biologics; dietary supplements; foods; alcohol; and tobacco. These sources were then examined for classification by severity of interaction and the underlying evidence base. This study provides evidence that there is little concordance among commonly used drug compendia and product labels with respect to interactions involving warfarin.

Recommendations for Generating, Evaluating, and Implementing Drug‐Drug Interaction Evidence

In October 2009, a 2‐day, multistakeholder, national conference was held in Rockville, Maryland, to discuss and propose methods to improve the drug‐drug interaction (DDI) evidence base and its evaluation and integration into clinical decision support (CDS) systems. The conference featured participants representing consumers, health care providers, those responsible for relevant policies and guidelines, and developers and vendors of DDI compendia, databases, and CDS systems. One desired outcome of the conference was to prepare recommendations on critical issues surrounding DDI evidence. A set of recommendations was developed to improve the generation, evaluation, and translation of DDI evidence into CDS systems based on presentations by experts and the supporting literature. These recommendations were reviewed initially by conference moderators, speakers, and Scientific Steering and Planning Committee members, and subsequently by all attendees. The following recommendations were developed to increase patient safety by improving the relevance and assessment of DDI evidence: conduct well‐designed studies to determine the incidence, outcomes, and patient‐level risk factors for DDIs; use a systematic and transparent process for evaluating the DDI evidence in order to estimate the severity and risks of DDIs; and improve the integration of DDI evidence into electronic CDS. Opportunities exist to improve the DDI evidence base, develop and promote a systematic approach for evaluating the evidence, and integrate this evidence into meaningful CDS.

Recommendations for selecting drug–drug interactions for clinical decision support

PURPOSE Recommendations for including drug-drug interactions (DDIs) in clinical decision support (CDS) are presented. SUMMARY A conference series was conducted to improve CDS for DDIs. A work group consisting of 20 experts in pharmacology, drug information, and CDS from academia, government agencies, health information vendors, and healthcare organizations was convened to address (1) the process to use for developing and maintaining a standard set of DDIs, (2) the information that should be included in a knowledge base of standard DDIs, (3) whether a list of contraindicated drug pairs can or should be established, and (4) how to more intelligently filter DDI alerts. We recommend a transparent, systematic, and evidence-driven process with graded recommendations by a consensus panel of experts and oversight by a national organization. We outline key DDI information needed to help guide clinician decision-making. We recommend judicious classification of DDIs as contraindicated and more research to identify methods to safely reduce repetitive and less-relevant alerts. CONCLUSION An expert panel with a centralized organizer or convener should be established to develop and maintain a standard set of DDIs for CDS in the United States. The process should be evidence driven, transparent, and systematic, with feedback from multiple stakeholders for continuous improvement. The scope of the expert panels work should be carefully managed to ensure that the process is sustainable. Support for research to improve DDI alerting in the future is also needed. Adoption of these steps may lead to consistent and clinically relevant content for interruptive DDIs, thus reducing alert fatigue and improving patient safety.

Critical issues associated with drug–drug interactions: Highlights of a multistakeholder conference

Although many potential drug–drug interactions (DDIs) are clinically inconsequential, DDI-associated harm does occur.[1][1]–[6][2] The magnitude of harm caused by DDIs is not precisely known, but research suggests that DDIs may be a significant public health issue.[2][3]–[6][2] Americans are

Healthcare Professional Students’ Knowledge of Drug-Drug Interactions

Objectives. To evaluate changes in medical, pharmacy, and nurse practitioner students’ drug-drug interaction (DDI) knowledge after attending an educational program. Design. A DDI knowledge assessment containing 15 different drug pairs was administered to participants before and after a 45-minute educational session. Evaluation. Pharmacy, medical, and nursing students scored significantly higher on the posttest assessment for DDI recognition (median change 3, 9, and 8, respectively) and management strategy (median change 5, 9, 8, respectively), indicating a significant improvement in DDI knowledge as a result of the educational session. Pharmacy students scored significantly higher on the pretest; however, no difference was observed between the students’ posttest scores. Posttest scores for all student groups were significantly greater than their respective pretest scores (p < 0.001). Conclusions. Significant improvement in healthcare professional students’ DDI knowledge was observed following participation in the educational session.

Medical, nursing, and pharmacy students' ability to recognize potential drug-drug interactions: a comparison of healthcare professional students.

Purpose: To evaluate and compare the drug–drug interaction (DDI) knowledge of pharmacy, medical, and nurse practitioner (NP) students who are beginning supervised clinical practice. Data sources: This study utilized a prospective evaluation of DDI knowledge among healthcare professional students who were currently enrolled in their final didactic year at the University of Arizona Colleges of Medicine, Pharmacy, or Nursings NP program. Students were asked to assess 15 drug pairs and to select an appropriate management strategy for each pair. The primary outcome measure was the ability to correctly categorize each drug pair into one of the five management responses. The secondary outcome measure was the number of clinically significant DDIs recognized. Conclusions: Pharmacy students demonstrated significantly better knowledge than medical and NP students with respect to identifying and selecting management strategies for possible DDIs. However, there is much room for improvement for all groups. Implications for practice: An increase in curricular content that focuses on DDIs has the potential to better prepare medical, pharmacy, and NP students for practice situations involving DDI alerts, and to increase the quality of patient care. Disclosure No relationship exists between any of the authors and any commercial entity or product mentioned in this article that might represent a conflict of interest. No inducements have been made by any commercial entity to submit the manuscript for publication.

Evaluation of a drug-drug interaction: fax alert intervention program

BackgroundClinicians often encounter information about drug-drug interactions (DDIs) during clinical practice. This information is found within product information (hardcopy and electronic) and various electronic systems. Prescribers may receive medication-related communications in practice that are distributed by facsimile (fax), mail, or telephone from pharmacies and pharmacy benefit managers (PBMs). The purpose of this study was to determine if near-real time fax alerts for potential drug-drug interactions (PDDIs) would influence prescribing.MethodsA prospective study, in cooperation with a pharmacy benefit manager (PBM), was conducted targeting 18 clinically important PDDIs. Fax alerts included an individualized letter to the prescriber with a list of the interacting drugs, PDDI evidence summaries with citations, and recommended clinical management strategies. Among the 18 PDDIs, 13 PDDIs could be assessed for prescription therapy changes using pharmacy claims data. A prospective cohort design was used to evaluate changes in prescription dispensing 90-days following a PDDI fax alert.ResultsA total of 8,075 fax alerts were sent to prescribers and there were 4,712 alerts for the 13 PDDIs that could be assessed for change using pharmacy claims data. There were 2,019 patients (interventions) for which fax alerts were sent to their prescribers who were matched with a control group consisting of patients with the same PDDIs but for whom no fax alert was sent. Overall, this study found 154 (7.6%) of patients in the fax alert group compared to 132 (6.5%) in the control group had changes in therapy (p = 0.177).ConclusionsThis fax alert intervention program observed no statistically significant differences in prescribing with a fax alert compared to the control group. If PBMs chose to send individualized, evidence-based information to clinicians regarding drug-drug interactions, this study suggests it may not be an effective intervention to mitigate harm.